Mesenchymal stromal cells to protect kidney after traumatic hemorrhagic shock
Background & AimHaemorrhagic shock (HS) refers to the inadequate perfusion of tissues due to the imbalance between systemic oxygen delivery and consumption. Blunt or penetrating trauma is the most common cause of HS. The development of multiorgan failure after severe trauma is one of the leading...
Saved in:
Published in | Cytotherapy (Oxford, England) Vol. 21; no. 5; pp. S51 - S52 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
01.05.2019
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Background & AimHaemorrhagic shock (HS) refers to the inadequate perfusion of tissues due to the imbalance between systemic oxygen delivery and consumption. Blunt or penetrating trauma is the most common cause of HS. The development of multiorgan failure after severe trauma is one of the leading causes of morbidity and late mortality. Among critical organs, the Acute Kidney Injury (AKI) affects up to 50% of the patients and no etiologic treatment is available.Mesenchymal Stromal Cells (MSC) are multipotent cells found in a large number of adult tissues and used in clinical practice as a therapeutic agent for immunomodulation and tissue repair. Many studies have highlighted their immunomodulatory, anti-apoptotic/anti-oxidative stress, pro-angiogenic effect, stimulation of endogenous regenerative process or anti-fibrotic effect by direct contact or by secreting bioactive molecules. Our objective was to evaluate and optimize an early MSC therapy after traumatic hemorrhagic shock (THS) inducing an AKI.Methods, Results & ConclusionWe have developed in vivo THS model and validated functional assays on cultures of immune and renal human cells. In vivo, rats were subjected to 1h of HS at a Mean Arterial Pressure of 30mmHg, associated with administration of 1ml plasma from THS animals. Biological and histological analyses are currently performed on D2, D7 and D21. In vitro, a cellular model of renal injury was developed by adding a "shock cocktail" (SC) containing inflammatory cytokines, HMGB1, histones and H 2O 2. Several criteria have been studied: Membrane polarization of the mitochondria by the JC1 dye, MitoSOX and CellROX probes to evaluate the mitochondrial and cytoplasmic oxidation state. Aggression of renal cells induced a decrease in the mitochondrial membrane polarization. The CellROX probe also showed an increase in cytoplasmic oxidative stress. We also developed a model of inflammation using THP1 cell line treated with SC. The SC induced an increase in TNFα secretion by THP1. Our main preliminary results indicated that MSCs improved the viability of renal cells, partially restored their mitochondrial membrane potential and decreased their cytoplasmic oxidative stress. In addition, they can exert an anti-inflammatory effect by inhibited the secretion of TNFα by THP1 and increased their secretion of the anti-inflammatory cytokine IL1RA. Finally, the pre-clinical model mimicking a polytrauma could be a formidable tool to evaluate the benefit of MSC therapy, away from shock. |
---|---|
AbstractList | Haemorrhagic shock (HS) refers to the inadequate perfusion of tissues due to the imbalance between systemic oxygen delivery and consumption. Blunt or penetrating trauma is the most common cause of HS. The development of multiorgan failure after severe trauma is one of the leading causes of morbidity and late mortality. Among critical organs, the Acute Kidney Injury (AKI) affects up to 50% of the patients and no etiologic treatment is available.
Mesenchymal Stromal Cells (MSC) are multipotent cells found in a large number of adult tissues and used in clinical practice as a therapeutic agent for immunomodulation and tissue repair. Many studies have highlighted their immunomodulatory, anti-apoptotic/anti-oxidative stress, pro-angiogenic effect, stimulation of endogenous regenerative process or anti-fibrotic effect by direct contact or by secreting bioactive molecules. Our objective was to evaluate and optimize an early MSC therapy after traumatic hemorrhagic shock (THS) inducing an AKI.
We have developed in vivo THS model and validated functional assays on cultures of immune and renal human cells. In vivo, rats were subjected to 1h of HS at a Mean Arterial Pressure of 30mmHg, associated with administration of 1ml plasma from THS animals. Biological and histological analyses are currently performed on D2, D7 and D21. In vitro, a cellular model of renal injury was developed by adding a "shock cocktail" (SC) containing inflammatory cytokines, HMGB1, histones and H2O2. Several criteria have been studied: Membrane polarization of the mitochondria by the JC1 dye, MitoSOX and CellROX probes to evaluate the mitochondrial and cytoplasmic oxidation state. Aggression of renal cells induced a decrease in the mitochondrial membrane polarization. The CellROX probe also showed an increase in cytoplasmic oxidative stress. We also developed a model of inflammation using THP1 cell line treated with SC. The SC induced an increase in TNFα secretion by THP1. Our main preliminary results indicated that MSCs improved the viability of renal cells, partially restored their mitochondrial membrane potential and decreased their cytoplasmic oxidative stress. In addition, they can exert an anti-inflammatory effect by inhibited the secretion of TNFα by THP1 and increased their secretion of the anti-inflammatory cytokine IL1RA. Finally, the pre-clinical model mimicking a polytrauma could be a formidable tool to evaluate the benefit of MSC therapy, away from shock. Background & AimHaemorrhagic shock (HS) refers to the inadequate perfusion of tissues due to the imbalance between systemic oxygen delivery and consumption. Blunt or penetrating trauma is the most common cause of HS. The development of multiorgan failure after severe trauma is one of the leading causes of morbidity and late mortality. Among critical organs, the Acute Kidney Injury (AKI) affects up to 50% of the patients and no etiologic treatment is available.Mesenchymal Stromal Cells (MSC) are multipotent cells found in a large number of adult tissues and used in clinical practice as a therapeutic agent for immunomodulation and tissue repair. Many studies have highlighted their immunomodulatory, anti-apoptotic/anti-oxidative stress, pro-angiogenic effect, stimulation of endogenous regenerative process or anti-fibrotic effect by direct contact or by secreting bioactive molecules. Our objective was to evaluate and optimize an early MSC therapy after traumatic hemorrhagic shock (THS) inducing an AKI.Methods, Results & ConclusionWe have developed in vivo THS model and validated functional assays on cultures of immune and renal human cells. In vivo, rats were subjected to 1h of HS at a Mean Arterial Pressure of 30mmHg, associated with administration of 1ml plasma from THS animals. Biological and histological analyses are currently performed on D2, D7 and D21. In vitro, a cellular model of renal injury was developed by adding a "shock cocktail" (SC) containing inflammatory cytokines, HMGB1, histones and H 2O 2. Several criteria have been studied: Membrane polarization of the mitochondria by the JC1 dye, MitoSOX and CellROX probes to evaluate the mitochondrial and cytoplasmic oxidation state. Aggression of renal cells induced a decrease in the mitochondrial membrane polarization. The CellROX probe also showed an increase in cytoplasmic oxidative stress. We also developed a model of inflammation using THP1 cell line treated with SC. The SC induced an increase in TNFα secretion by THP1. Our main preliminary results indicated that MSCs improved the viability of renal cells, partially restored their mitochondrial membrane potential and decreased their cytoplasmic oxidative stress. In addition, they can exert an anti-inflammatory effect by inhibited the secretion of TNFα by THP1 and increased their secretion of the anti-inflammatory cytokine IL1RA. Finally, the pre-clinical model mimicking a polytrauma could be a formidable tool to evaluate the benefit of MSC therapy, away from shock. |
Author | Aussel, C Grosbot, M Banzet, S Baudry, N Peltzer, J Allain, E Vicaut, E |
Author_xml | – sequence: 1 fullname: Peltzer, J – sequence: 2 fullname: Aussel, C – sequence: 3 fullname: Baudry, N – sequence: 4 fullname: Allain, E – sequence: 5 fullname: Grosbot, M – sequence: 6 fullname: Vicaut, E – sequence: 7 fullname: Banzet, S |
BookMark | eNp9kM1Kw0AUhQepYKu-gKu8QOL8JJMERJDiH7S4UNfD5ObGTJpmysxUyNubUFcuXJ2zOZf7fSuyGOyAhNwwmjDK5G2XdDCGhFNWJlQkKZNnZMnSPI95JuVi7jKLBU_LC7LyvqOU06LIlmS7RY8DtONe95EPzs4J2Pc-CjY6OBsQQrQz9YBjpJuALgpOH_c6GIha3FvnWv01dd9a2F2R80b3Hq9_85J8Pj1-rF_izdvz6_phEwPLmIxRCuA0l5KXIEpBGaNZVQjNK0qBYdpURV3RptG1RtEIwLqGoshFUVWQ57UUl4Sf7oKz3jts1MGZvXajYlTNQlSnZiFqFqKoUJOQaXR3GuH02bdBpzyYiR1r4yZIVVvz__z-zxx6MxjQ_Q5H9J09umFiVkx5rqh6n43PwtkEmMk8Ez_J5oI2 |
ContentType | Journal Article |
Copyright | 2019 |
Copyright_xml | – notice: 2019 |
DBID | AAYXX CITATION |
DOI | 10.1016/j.jcyt.2019.03.416 |
DatabaseName | CrossRef |
DatabaseTitle | CrossRef |
DatabaseTitleList | |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Pharmacy, Therapeutics, & Pharmacology |
EISSN | 1477-2566 |
EndPage | S52 |
ExternalDocumentID | 10_1016_j_jcyt_2019_03_416 S1465324919305675 1_s2_0_S1465324919305675 |
GroupedDBID | --- --M .1- .FO .~1 1P~ 1~. 29F 36B 4.4 457 4G. 53G 5GY 5VS 7-5 8P~ AAAJQ AACTN AAEDT AAEDW AAIKJ AAKOC AALRI AAOAW AAXKI AAXUO ABDBF ABGSF ABJNI ABMAC ABMZM ABUDA ABXDB ACDAQ ACGEJ ACGFS ACRLP ADBBV ADCVX ADEZE ADXPE AEBSH AEHWI AEKER AENEX AEVXI AFCTW AFJKZ AFKVX AFKWA AFRHN AFTJW AFXIZ AGEKW AGHFR AGRDE AGUBO AGYEJ AIEXJ AIKHN AITUG AJOXV AJRQY AJUYK AJWEG AKRWK ALMA_UNASSIGNED_HOLDINGS AMFUW AMRAJ ANZVX ASPBG AVWKF AWYRJ AXJTR AZFZN BKOJK BLXMC BNPGV CAG CJTIS COF CS3 DU5 EAP EBC EBS EFJIC EJD EMB EMK EMOBN ESX F5P FDB FEDTE FGOYB FIRID FNPLU FYGXN GBLVA H13 HVGLF HZ~ KOM LUGTX M44 MO0 O-L O9. OAUVE OK~ P-8 P-9 P2P PC. Q38 R2- ROL SDF SPCBC SSH SSI SSU SSZ SV3 T5K TDBHL TFW Z5R ~G- AAIAV ABLVK ABYKQ AJBFU DOVZS EFLBG LCYCR AAYXX CITATION |
ID | FETCH-LOGICAL-c1516-e63c2076629c39301105b83a2b00c1e4fb8db0ffadae3f3ceddc88738bbc77d63 |
IEDL.DBID | AIKHN |
ISSN | 1465-3249 |
IngestDate | Fri Dec 06 03:34:15 EST 2024 Fri Feb 23 02:16:03 EST 2024 Tue Oct 15 22:56:13 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 5 |
Language | English |
License | https://www.elsevier.com/tdm/userlicense/1.0 |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c1516-e63c2076629c39301105b83a2b00c1e4fb8db0ffadae3f3ceddc88738bbc77d63 |
ParticipantIDs | crossref_primary_10_1016_j_jcyt_2019_03_416 elsevier_sciencedirect_doi_10_1016_j_jcyt_2019_03_416 elsevier_clinicalkeyesjournals_1_s2_0_S1465324919305675 |
PublicationCentury | 2000 |
PublicationDate | May 2019 |
PublicationDateYYYYMMDD | 2019-05-01 |
PublicationDate_xml | – month: 05 year: 2019 text: May 2019 |
PublicationDecade | 2010 |
PublicationTitle | Cytotherapy (Oxford, England) |
PublicationYear | 2019 |
Publisher | Elsevier Inc |
Publisher_xml | – name: Elsevier Inc |
SSID | ssj0020885 |
Score | 2.2614846 |
Snippet | Background & AimHaemorrhagic shock (HS) refers to the inadequate perfusion of tissues due to the imbalance between systemic oxygen delivery and consumption.... Haemorrhagic shock (HS) refers to the inadequate perfusion of tissues due to the imbalance between systemic oxygen delivery and consumption. Blunt or... |
SourceID | crossref elsevier |
SourceType | Aggregation Database Publisher |
StartPage | S51 |
SubjectTerms | Advanced Basic Science Other |
Title | Mesenchymal stromal cells to protect kidney after traumatic hemorrhagic shock |
URI | https://www.clinicalkey.es/playcontent/1-s2.0-S1465324919305675 https://dx.doi.org/10.1016/j.jcyt.2019.03.416 |
Volume | 21 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT4NAEJ74uHgxPmN9ZQ_Gi2JZFthybIymato0URNvG3bZTauxbQo9cPG3OwuLj2g8eCKQLJAP5vt2YeYbgBM_UtqozHimoxIP9TbwZKaUJ2liOEfN1lXTvv4g7j2Gt0_R0xJcNrUwNq3ScX_N6RVbuyNth2Z7Nh6376m1BsPVA05BUMV5tAyrKEf2X-1q9-auN_hYd2EgRXWRUeTZAa52pk7zelalTamklddpaNue_6ZPXzTnegPW3WSRdOv72YQlPdmC02HtNl2ek4fP4qn8nJyS4acPdbkN_b6tLFKj8hXPkRfzqd3aD_U5KabEGTSQl3E20SWpeoWTYp4uKg9XMrIZuPNRisRI8hGS5g48Xl89XPY81z3BU6jisadjpgKfx3GQKJbYOPYj2WFpgIGmqA6N7GTSNybNUs0MQ7wzhYzDOlIqzrOY7cLKZDrRe0BoYKjhsS-ZkWGqgpSyMMWVZaZDmSRcteCswUzMapMM0WSPPQuLsLAIC58JRLgFvIFVNOWfSFg6d9GTCyryQPjixxNuQfQx8ttLIpD__7ji_j_HHcCa3avzGw9hpZgv9BHOQQp5DMsXb_TYvWnvu0vdlQ |
link.rule.ids | 314,780,784,4502,24116,27924,27925,45585,45679 |
linkProvider | Elsevier |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV07T8MwED5BGWBBPEV5ekAsNDSJk7gZUUVVoEVIFKmbFTu22iJa1IQhC7-dcx4tCMTAFCmJk-iL77uz9d0dwLntS6VlrC3dkqGF_ta1RCylJZxQM4Y-W-VN-_oPQffZuxv6wxVoV7kwRlZZcn_B6Tlbl2eaJZrNt_G4-eSY0mC4esAQBL0481dhzfMx-sVJffWx0Hm4aEZ-kWLkW-b2MnOmEHlNZGYElU5e6dQzTc9_805fPE5nCzbLUJFcF1-zDStqugMXj0Wt6axBBsvUqaRBLsjjsgp1tgv9vskrkqPsFZ-RpPOZOZpt-oSkM1KWZyAv43iqMpJ3CifpPHrPK7iSkdHfzkcR0iJJRkiZe_DcuRm0u1bZO8GS6MMDSwVUujYLAjeUNDRWbPuiRSMXzUw6ytOiFQtb6yiOFNUU0Y4l8g1tCSEZiwO6D7XpbKoOgDiudjQLbEG18CLpRg71IlxXxsoTYchkHS4rzPhbUSKDV9qxCTcIc4MwtylHhOvAKlh5lfyJdKWS0nYS7vDE5Tb_8X_r4C9GfpsiHNn_jzce_nPcGax3B_0e790-3B_BhrlSKB2PoZbO39UJRiOpOM1n2ye9B95u |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mesenchymal+stromal+cells+to+protect+kidney+after+traumatic+hemorrhagic+shock&rft.jtitle=Cytotherapy+%28Oxford%2C+England%29&rft.au=Peltzer%2C+J&rft.au=Aussel%2C+C&rft.au=Baudry%2C+N&rft.au=Allain%2C+E&rft.date=2019-05-01&rft.issn=1465-3249&rft.volume=21&rft.issue=5&rft.spage=S51&rft.epage=S52&rft_id=info:doi/10.1016%2Fj.jcyt.2019.03.416&rft.externalDBID=ECK1-s2.0-S1465324919305675&rft.externalDocID=1_s2_0_S1465324919305675 |
thumbnail_m | http://utb.summon.serialssolutions.com/2.0.0/image/custom?url=https%3A%2F%2Fcdn.clinicalkey.com%2Fck-thumbnails%2F14653249%2FS1465324919X00067%2Fcov150h.gif |